Rob Lowe and Rashida Jones will leave the series after the 13th episode of the upcoming sixth season.
They play characters Chris Traeger and Ann Perkins.
The news was first reported by Buzzfeed.
In an email, executive producer Mike Schur, said: "Heading into this year, with the two of them contemplating parenthood, it felt like the natural time to move them into the next phase."
On "Parks and Rec," their characters dated on and off and have decided to try to have a baby together.
"Parks and Recreation" also stars Amy Poehler, Nick Offerman, Aubrey Plaza and Aziz Ansari as employees working in local government in Indiana.
Jones has been on the series since its first episode. Lowe joined the show in season two.
This isn't the first time Lowe has left a TV series before it went off the air. He left NBC's "The West Wing" and ABC's "Brothers and Sisters" after four seasons.